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Kim Fox,
Michel Komajda,
Ian Ford,
Michele Robertson,
Michael Böhm, Jeffrey S Borer,
Philippe Gabriel Steg,
Luigi Tavazzi,
Michal Tendera,
Roberto Ferrari,
Karl Swedberg
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ABSTRACT: AimsTo test the effect of ivabradine on the outcomes in a broad population with left-ventricular (LV) systolic dysfunction with coronary artery disease (CAD) and/or heart failure (HF).Methods and resultsIndividual trial data from BEAUTIFUL and SHIFT were pooled to evaluate the effect of ivabradine on the outcomes in patients with LV dysfunction and heart rate ≥70 b.p.m. The pooled population (n = 11 897; baseline age 62.3 ± 10.4 years, heart rate 79.6 ± 9.2 b.p.m., and LV ejection fraction 30.3 ± 5.6%) was well treated according to current recommendations (87% beta-blockers, 90% renin-angiotensin system inhibitors). Median follow-up was 21 months. Treatment with ivabradine was associated with a 13% relative risk reduction for the composite of cardiovascular mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF hospitalizations (19%, P < 0.001). There were also significant relative risk reductions for the composite of cardiovascular mortality, HF hospitalizations, or myocardial infarction (MI) hospitalization (15%, P < 0.001); cardiovascular mortality and non-fatal MI (10%, P = 0.023); and MI hospitalization (23%, P = 0.009). Similar results were found in patients with differing clinical profiles. Ivabradine was well tolerated.Conclusion
Ivabradine may be important for the improvement of clinical outcomes in patients with LV systolic dysfunction and heart rate ≥70 b.p.m., whatever the primary clinical presentation (CAD or HF) or clinical status (NYHA class).
European Heart Journal 03/2013; · 10.48 Impact Factor
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Phyllis G Supino,
Ofek Y Hai,
Tajinderpal S Saraon,
Edmund M Herrold,
Monica Diaz,
Nasimullah Khan,
Clare A Hochreiter,
Paul D Kligfield,
Karl H Krieger,
Leonard N Girardi,
O Wayne Isom, Jeffrey S Borer
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ABSTRACT: Exercise duration during exercise treadmill testing (ETT) predicts long-term outcome among asymptomatic patients with mitral regurgitation. However, the prognostic value of preoperative exercise duration in patients who undergo mitral valve surgery is unknown. We examined findings among 45 prospectively followed (average 9.2 ± 4.3 years) patients (aged 54.8 ± 12.0 years, 45% men) with chronic isolated severe MR who underwent ETT before mitral valve surgery to test the hypotheses that exercise duration predicts long-term postoperative survival and persistent symptoms within 2 years after operation. During follow-up, 11 patients died; of these, 8 had persistent symptoms. Among patients who exercised >7 minutes, average annual postoperative all-cause and cardiovascular mortality risks were 0.75% (both endpoints) versus 5.4% and 4.8%, respectively, versus those who exercised ≤7 minutes (p = 0.003 all-cause, p = 0.007 cardiovascular). Exercise duration predicted postoperative deaths (p <.02 all cause, p <.04 cardiovascular) even when analysis was adjusted for preoperative variations in age, gender, medications, history of atrial fibrillation, and peak exercise heart rates. Other ETT, echocardiographic, and clinical variables were not independently associated with these outcomes when exercise duration was considered in the analysis. Preoperative exercise duration also predicted postoperative (New York Heart Association functional class ≥II) symptom persistence (p = 0.012), whereas other ETT, echocardiographic and clinical variables did not (NS, all). In conclusion, among patients who undergo surgery for chronic nonischemic mitral regurgitation, preoperative exercise duration, unlike many commonly used descriptors, is useful for predicting postoperative mortality and symptom persistence. Future research should determine whether interventions to improve exercise tolerance before mitral valve surgery can modify these postoperative outcomes.
The American journal of cardiology 03/2013; · 3.58 Impact Factor
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ABSTRACT: AIMS: We explored the impact of being hospitalized due to worsening heart failure (WHF) or a myocardial infarction (MI) on subsequent mortality in a large contemporary data set of patients with stable chronic systolic heart failure (HF). METHODS AND RESULTS: A total of 6558 patients with stable systolic HF, 6505 with analysable data, with an EF of ≤35%, who were included in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT), were followed for a median of 22.9 months with respect to hospitalizations and vital status. Among the 1288 patients who had at least one hospitalization due to WHF or MI, 455 (35.3%) died during follow-up compared with 600 (11.5%) among patients not hospitalized for these reasons. The risk for death was highest in the early phase after hospitalization. The risk declined rapidly during the first month but remained 3.5-fold (95% confidence interval 2.3-5.1) increased at 18 months after a first WHF hospitalization and 8.8-fold (95% confidence interval 3.6-21.6) increased at 18 months after a first MI hospitalization. CONCLUSION: The present study confirms previous findings that in patients with stable chronic systolic HF, a hospitalization for WHF or MI is associated with substantially increased risk for subsequent death even with contemporary extensive background pharmacological therapy. The risk is most pronounced in the early phase of hospitalization but remains elevated even after 18 months. Preventing HF hospitalization appears as an important therapeutic objective in such patients, and a hospitalization for WHF or MI should lead to a careful therapeutic reassessment.
European Journal of Heart Failure 03/2013; · 4.90 Impact Factor
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Oladipupo Olafiranye,
Clare A Hochreiter, Jeffrey S Borer,
Phyllis G Supino,
Edmund M Herrold,
Adam S Budzikowski,
Ofek Y Hai,
Dany Bouraad,
Paul D Kligfield,
Leonard N Girardi,
Karl H Krieger,
O Wayne Isom
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ABSTRACT: Background: Nonsustained ventricular tachycardia (VT), frequent in unoperated severe mitral regurgitation (MR), confers mortality risk [sudden death (SD) and cardiac death (CD)]. The prognostic value of VT after mitral valve surgery (MVS) is unknown; we aimed to define this prognostic value and to assess its modulation by left (LV) and/or right (RV) ventricular ejection fraction (EF) for mortality after MVS. Methods: In 57 patients (53% females, aged 58 ± 12 years) with severe MR prospectively followed before and after MVS, we performed 24-hour ambulatory electrocardiograms approximately annually. LVEF and RVEF were determined within 1 year after MVS by radionuclide cineangiography. Results: During 9.52 ± 3.49 endpoint-free follow-up years, late postoperative CD occurred in 11 patients (7 SD, 4 heart failures). In univariable analysis, >1 VT episode after MVS predicted SD (p < 0.01) and CD (SD or heart failure; p < 0.04). Subnormal postoperative RVEF predicted CD (p < 0.04). When adjusted for preoperative age, gender, etiology or antiarrhythmics, both postoperative VT and RVEF predicted CD (p ≤ 0.05). When postoperative VT and RVEF were both in the multivariable model, only subnormal RVEF predicted CD (p < 0.04). Among those with normal RVEF, VT >1 episode predicted SD (p = 0.03). Conclusion: Postoperative VT and subnormal RVEF predict late postoperative deaths in nonischemic MR. Their assessment may aid patient management.
Cardiology 02/2013; 124(2):108-115. · 1.71 Impact Factor
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ABSTRACT: AimsWe explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial.Methods and resultsSHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized β-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65-0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55-0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54-0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations.Conclusion
Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.
European Heart Journal 08/2012; · 10.48 Impact Factor
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ABSTRACT: During the past 2 decades, percutaneous coronary intervention (PCI) has increased dramatically compared with coronary artery bypass grafting (CABG) for patients with coronary artery disease. However, although the evidence available to all practitioners is similar, the relative distribution of PCI and CABG appears to differ among hospitals and regions.
We reviewed the published data from the mandatory New York State Department of Health annual cardiac procedure reports issued from 1994 through 2008 to define trends in PCI and CABG utilization in New York and to compare the PCI/CABG ratios in the metropolitan area to the remainder of the State. During this 15-year interval, the procedure volume changes for CABG, for all cardiac surgeries, for non-CABG cardiac surgeries, and for PCI for New York State were -40%, -20%, +17.5%, and +253%, respectively; for the Manhattan programs, the changes were similar as follows: -61%, -23%, +14%, and +284%. The average PCI/CABG ratio in New York State increased from 1.12 in 1994 to 5.14 in 2008; however, in Manhattan, the average PCI/CABG ratio increased from 1.19 to 8.04 (2008 range: 3.78 to 16.2). The 2008 PCI/CABG ratios of the Manhattan programs were higher than the ratios for New York City programs outside Manhattan, in Long Island, in the northern counties contiguous to New York City, and in the rest of New York State; their averages were 5.84, 5.38, 3.31, and 3.24, respectively. In Manhattan, a patient had a 56% greater chance of receiving PCI than CABG as compared with the rest of New York State; in one Manhattan program, the likelihood was 215% higher.
There are substantial regional and statewide differences in the utilization of PCI versus CABG among cardiac centers in New York, possibly related to patient characteristics, physician biases, and hospital culture. Understanding these disparities may facilitate the selection of the most appropriate, effective, and evidence-based revascularization strategy. (J Am Heart Assoc. 2012;1:e001446 doi: 10.1161/JAHA.112.001446.).
Journal of the American Heart Association. 04/2012; 1(2):e001446.
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Circulation Heart Failure 03/2012; 5(2):294-302. · 6.29 Impact Factor
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ABSTRACT: The SHIFT echocardiographic substudy evaluated the effects of ivabradine on left ventricular (LV) remodelling in heart failure (HF).
Eligible patients had chronic HF and systolic dysfunction [LV ejection fraction (LVEF) ≤35%], were in sinus rhythm, and had resting heart rate ≥70 bpm. Patients were randomly allocated to ivabradine or placebo, superimposed on background therapy for HF. Complete echocardiographic data at baseline and 8 months were available for 411 patients (ivabradine 208, placebo 203). Treatment with ivabradine reduced LVESVI (primary substudy endpoint) vs. placebo [-7.0 ± 16.3 vs. -0.9 ± 17.1 mL/m(2); difference (SE), -5.8 (1.6), 95% CI -8.8 to -2.7, P< 0.001]. The reduction in LVESVI was independent of beta-blocker use, HF aetiology, and baseline LVEF. Ivabradine also improved LV end-diastolic volume index (-7.9 ± 18.9 vs. -1.8 ± 19.0 mL/m(2), P= 0.002) and LVEF (+2.4 ± 7.7 vs. -0.1 ± 8.0%, P< 0.001). The incidence of the SHIFT primary composite outcome (cardiovascular mortality or hospitalization for worsening HF) was higher in patients with LVESVI above the median (59 mL/m2) at baseline (HR 1.62, 95% CI 1.03-2.56, P= 0.04). Patients with the largest relative reductions in LVESVI had the lowest event rates.
Ivabradine reverses cardiac remodelling in patients with HF and LV systolic dysfunction.
European Heart Journal 08/2011; 32(20):2507-15. · 10.48 Impact Factor
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ABSTRACT: Heart failure (HF) has a major impact on health-related quality of life (HQoL). The aim was to evaluate whether heart rate (HR) reduction with ivabradine can translate into increased HQoL in parallel to a reduction of primary outcomes in SHIFT.
In symptomatic patients with systolic HF treated with recommended background therapy, HQoL was assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) containing the following dimensions: overall summary score (OSS) and clinical summary score (CSS), analysed at baseline, and 4, 12, and 24 months, and last post-baseline visit. A total of 1944 patients (968 ivabradine, 976 placebo) were evaluated. At 12 months, incidence of clinical events (cardiovascular death or hospital admission for HF) was inversely associated with KCCQ scores. Ivabradine reduced HR by 10.1 bpm (placebo-corrected, P < 0.001) and improved KCCQ by 1.8 for CSS and 2.4 for OSS (placebo-corrected, P = 0.02 and P < 0.01, respectively); these changes were associated with the change in HR for both CSS (P < 0.001) and OSS (P < 0.001). The relationship was found in both allocation groups though the changes were more pronounced in the ivabradine group. Health-related quality of life at follow-up was better preserved in the ivabradine group compared with placebo; poorest outcomes were seen in the placebo group with lowest KCCQ scores (<50).
In patients with systolic HF, low HQoL is associated with an increased rate of cardiovascular death or hospital admission for HF. Reduction in HR with ivabradine is associated with improved HQoL. The magnitude of HR reduction is related to the extent of improvement in HQoL.
European Heart Journal 08/2011; 32(19):2395-404. · 10.48 Impact Factor
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ABSTRACT: Heart rate influences myocardial oxygen demand, coronary blood flow, and myocardial function. Clinical and experimental studies support an association between elevated resting heart rate and a broad range of maladaptive effects on the function and structure of the cardiovascular system. Heart rate has been shown to be an important predictor of mortality in cardiovascular disorders such as coronary artery disease, myocardial infarction, and chronic heart failure. This review summarizes the specific influence of heart rate on vascular morphology and function as well as on myocardial lesions leading from early impact on vascular homeostasis to myocardial hemodynamics in chronic heart failure. Heart rate can be easily determined during physical examination of the patient and therefore allows a simple hint on prognosis and efficiency of therapy.
Clinical Research in Cardiology 01/2011; 100(1):11-9. · 2.95 Impact Factor
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ABSTRACT: Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure.
Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960.
6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 [21%] placebo vs 514 [16%] ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151 [5%] vs 113 [3%]; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0.0001).
Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder.
Servier, France.
The Lancet 09/2010; 376(9744):875-85. · 38.28 Impact Factor
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ABSTRACT: Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population.
We analysed cardiovascular outcomes in the placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided by quintiles of baseline heart rate in the placebo group. The primary composite endpoint was cardiovascular death or hospital admission for worsening heart failure. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes. Analysis adjusted to change in heart rate was used to study heart-rate reduction as mechanism for risk reduction by ivabradine directly.
In the placebo group, patients with the highest heart rates (>or=87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2.34, 95% CI 1.84-2.98, p<0.0001). Risk of primary composite endpoint events increased by 3% with every beat increase from baseline heart rate and 16% for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17.4%, 95% CI 15.3-19.6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0.95, 0.85-1.06, p=0.352).
Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure.
Servier, France.
The Lancet 09/2010; 376(9744):886-94. · 38.28 Impact Factor
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ABSTRACT: Ivabradine is a specific heart rate-lowering antianginal agent that was evaluated in a clinical development program involving approximately 3,000 patients with stable coronary artery disease, most with angina pectoris. We analyzed the pharmacokinetics, efficacy (evaluated by exercise tolerance testing), safety, and effects on glucose metabolism of ivabradine in patients with diabetes mellitus (DM) in this program. Most analyses included data from 535 patients with DM, approximately 18% of the overall patient sample. Patients with DM were older, more likely to be women, and more likely to have more severe angina pectoris than patients without DM. The pharmacokinetics of ivabradine did not differ in patients with DM versus those without DM. A reduction in the heart rate at rest with ivabradine was similar in those with (15.2%) and without (15.7%) DM. At baseline, the exercise capacity tended to be lower in the patients with DM, but the improvements in most exercise tolerance measures with ivabradine treatment were similar in patients with and without DM. No special safety concerns were associated with ivabradine in those with DM. The rates of sinus bradycardia and visual disturbances, known to be related to the action of ivabradine, showed no relative increase in the patients with DM. Ivabradine treatment was not associated with adverse effects on glucose metabolism. In conclusion, ivabradine was effective in preventing angina in patients with DM and was not associated with particular safety concerns or adverse effects on glucose metabolism. Ivabradine represents an attractive alternative to beta blockers in patients with stable angina pectoris and DM.
The American journal of cardiology 01/2010; 105(1):29-35. · 3.58 Impact Factor
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ABSTRACT: AIMS: Elevated heart rate is a significant marker for mortality and morbidity in cardiovascular disease including heart failure. Despite background treatment with a beta-blocker, many patients with heart failure and low ejection fraction maintain a heart rate above 70 b.p.m. Ivabradine reduces heart rate directly through inhibition of the I(f) ionic current. Methods SHIFT is a randomized, double-blind study designed to compare ivabradine with placebo on outcomes in patients with symptomatic chronic heart failure (NYHA class II-IV), left-ventricular ejection fraction < or =35%, and a prior hospitalization for worsening heart failure within the previous 12 months. Randomized treatment is given on top of guidelines-based therapy for chronic heart failure, including a beta-blocker at optimized dose. Resting heart rate at baseline must be > or =70 b.p.m. The primary endpoint is the composite of the time to first event of cardiovascular death or hospitalization for worsening heart failure. Secondary endpoints include all-cause, cardiovascular and heart failure mortality, and hospitalization. The randomized treatment period lasts approximately 12-48 months. The study will include approximately 6500 patients and will continue until > or =1600 primary endpoints have occurred. The first patient was randomized in October 2006, and the study is expected to end in 2010. CONCLUSION: The SHIFT study will assess if a heart rate reduction by direct sinus node inhibition can reduce cardiovascular outcomes in patients with chronic heart failure and left-ventricular systolic dysfunction.
European Journal of Heart Failure 11/2009; 12(1):75-81. · 4.90 Impact Factor
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ABSTRACT: The antianginal and anti-ischemic efficacy of ivabradine has been demonstrated in large-scale trials. Pooling trial data allowed for subpopulation analyses of ivabradine's antianginal efficacy.
Data on the frequency of angina attacks, short-acting nitrate consumption, and heart rate were pooled from 5 randomized trials in patients with stable angina pectoris receiving 5, 7.5, or 10 mg of ivabradine b.i.d. for 3 or 4 months. The subpopulations were defined according to age, sex, disease characteristics, and comorbidities (severity of angina, history of myocardial infarction, cerebrovascular disease, revascularization status, diabetes, asthma/chronic obstructive pulmonary disease, or peripheral vascular disease).
Efficacy data were available for 2,425 patients (full analysis set), in whom ivabradine reduced the frequency of diary-based angina attacks by 59.4% and nitrate consumption by 53.7%. All subpopulations experienced 51-70% reductions in the frequency of angina attacks, with similar reductions for the other parameters studied. Ivabradine's efficacy was maintained in the presence of different comorbidities. In the safety set, ivabradine reduced heart rate by 14.5%. Ivabradine had a good safety and tolerability profile in all the subpopulations assessed.
The antianginal efficacy of ivabradine was consistent across all the subpopulations analyzed, independent of the severity of angina and the presence of a comorbidity.
Cardiology 06/2009; 114(2):116-25. · 1.71 Impact Factor
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Matthew C Becker,
Thomas H Wang,
Lisa Wisniewski,
Kathy Wolski,
Peter Libby,
Thomas F Lüscher, Jeffrey S Borer,
Alice M Mascette,
M Elaine Husni,
Daniel H Solomon,
David Y Graham,
Neville D Yeomans,
Henry Krum,
Frank Ruschitzka,
A Michael Lincoff,
Steven E Nissen
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ABSTRACT: Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain.
The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations.
PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.
American heart journal 05/2009; 157(4):606-12. · 4.65 Impact Factor
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ABSTRACT: Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS.
We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbach's alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002).
Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.
Journal of cardiac failure 05/2009; 15(3):267-77. · 3.25 Impact Factor
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Matthew D Bacchetta,
Arash Salemi,
Federico Milla,
Mun K Hong,
Fermin Tio,
Ying Zhou,
Rong Chen,
Edward Southard,
Leonard Y Lee,
Charles A Mack,
Karl H Krieger,
O Wayne Isom,
Wilson Ko, Jeffrey S Borer,
Daniel F Catanzaro
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ABSTRACT: The efficacy of vein grafts used in coronary and peripheral artery bypass is limited by excessive hyperplasia and fibrosis that occur early after engraftment. In the present study, we sought to determine whether low-dose spironolactone alleviates maladaptive vein graft arterialization and alters intimal reaction to coronary artery stenting. Yorkshire pigs were randomized to treatment with oral spironolactone 25 mg daily or placebo. All animals underwent right carotid artery interposition grafting using a segment of external jugular vein and, 5 days later, underwent angiography of carotid and coronary arteries. At that time, a bare metal stent was placed in the left anterior descending artery and balloon angioplasty was performed on the circumflex coronary artery. Repeat carotid and coronary angiograms were performed before euthanasia and graft excision at 30 days. Angiography revealed that venous grafts of spironolactone-treated animals had lumen diameters twice the size of controls at 5 days, a finding that persisted at 30 days. However, neointima and total vessel wall areas also were 2- to 3-fold greater in spironolactone-treated animals, and there were no differences in vessel wall layer thicknesses or collagen and elastin densities. In the coronary circulation, there were no differences between treatment groups in any vessel wall parameters in either stented or unstented vessels. Taken together, these observations suggest that low-dose spironolactone may exert a novel protective effect on remodeling in venous arterial grafts that does not depend on the reduction of hyperplastic changes but may involve dilatation of the vessel wall.
American journal of therapeutics 04/2009; 16(3):204-14.
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Current Diabetes Reports 03/2009; 9(1):1-3. · 2.50 Impact Factor
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ABSTRACT: In aortic regurgitation (AR), fibronectin (FN) expression is upregulated. This study sought to determine signal transduction pathways involved in upregulation of FN expression in AR.
Cardiac fibroblasts (CF) from rabbits with surgically induced AR and matched controls (NL) were cultured and assayed for FN expression and kinase activity with and without inhibitors of kinases JNK, p38 mitogen-activated protein kinase (MAPK) and extracellular response kinase (ERK). NL CF also were subjected to cyclic strain mimicking AR for 24 h in culture with and without inhibitors.
AR CF exhibited 2.9-fold greater c-Jun phosphorylation (p < 0.01) and 1.5- to 2-fold greater ATF2 phosphorylation (p < 0.05-0.01) than NL. JNK and p38MAPK inhibition reduced c-Jun and ATF2 phosphorylation to NL; ERK inhibition had no effect. FN mRNA expression was similar in pattern to kinase activities. Cyclic strain in NL CF increased c-Jun phosphorylation 2-fold versus unstrained controls (p < 0.005). This was suppressed by inhibition of JNK but not p38MAPK.
FN expression in response to the acute mechanical strain resembling AR is upregulated primarily via JNK. However, in chronic AR both JNK and p38MAPK are involved. These signaling pathways represent potential therapeutic targets for normalizing extracellular matrix (ECM) composition and contractile force transmission, believed to be related to ECM composition/organization, in AR.
Cardiology 03/2009; 113(4):291-8. · 1.71 Impact Factor
